3-methylcholanthrene activates human immunodeficiency virus type 1 replication via aryl hydrocarbon receptor

Microbiol Immunol. 2003;47(5):363-70. doi: 10.1111/j.1348-0421.2003.tb03408.x.


We found that 3-methylcholanthrene (3-MC) could induce the reactivation of human immunodeficiency virus type 1 (HIV-1) replication in OM 10.1 cell, promyelocytic cell line latently infected with HIV-1. Transient luciferase expression experiments have revealed no particular transcription factors that are responsible for the effect of 3-MC in inducing HIV-1 gene expression as HIV-1 LTR mutants lacking various upstream transcriptional activators similarly responded to 3-MC. In addition, there was no effect of 3-MC on the DNA binding activity of nuclear factor-kappa B (NF-kappaB) that was previously reported to be crucial for the effect of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), a chemical homologue of 3-MC. However, overexpression of wild type aryl hydrocarbon receptor (AhR), a nuclear receptor of polycyclic aromatic hydrocarbons (PAHs) such as 3-MC, augmented the effect of 3-MC in the induction of gene expression from HIV-1 LTR. Moreover, a dominant negative mutant of AhR dramatically reduced the 3-MC-mediated activation of HIV-1 LTR. These findings suggest that 3-MC stimulates HIV-1 transcription by interacting with general transcription factors. Our observations indicate that chronic exposure of the HIV-1 infected individuals to PAHs may be contributable to the clinical development of acquired immunodeficiency syndrome (AIDS) among the individuals infected with HIV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Line, Transformed
  • HIV Long Terminal Repeat / genetics
  • HIV Long Terminal Repeat / physiology
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Methylcholanthrene / pharmacology*
  • Mutation
  • NF-kappa B / metabolism
  • Polychlorinated Dibenzodioxins / pharmacology
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Tumor Cells, Cultured
  • Virus Activation
  • Virus Latency*
  • Virus Replication / drug effects*


  • NF-kappa B
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon
  • Methylcholanthrene